Process of producing catechol derivatives

ABSTRACT

An improved process for producing a catechol derivative (1) useful as a intermediate of pharmaceuticals and agricultural chemicals, being shown by the following reaction scheme. The process is characterized in that formulation in the first step is carried out in the two stages, that is, the reaction is carried out in the presence of a tin catalyst at 60-85° C. to a conversion of 30 to 80% and then is completed at 95-105° C. to produce a salicylaldehyde derivative (3) in a high yield and a high selectivity. Thereby, the objective catechol derivative (1) can be obtained in a high yield and with a high purity. ##STR1## In the above formula, R is alkyl, cycloalkyl, aralkyl, alkoxy, halogen atom, allyl, or aryl, and R 1  is a hydroxy protective group.

This is the U.S. National Stage Application of PCT/JP96/03650 filed Dec.13, 1996 now WO 97/22574 published Jun. 26, 1997.

TECHNICAL FIELD

This invention relates to an improved process for preparing a catecholderivative represented by a generic formula (1) mentioned later, whichconstitutes a basic structure of a compound useful especially forpharmaceuticals and agricultural chemicals and is used as anintermediate thereof.

BACKGROUND ART

Monoalkylcatechol derivatives are used as intermediates forpharmaceuticals and agricultural chemicals. The method of preparing themby alkyl-etherification of only a hydroxy group on one side of acorresponding catechol derivative and the method of preparing them byhydroxylation of a corresponding alkoxybenzene derivative have beenmainly known. As to the former, the alkyl-ether method by dialkylsulfate (Japanese Patent Publication (A) No. 112485/1993), and thealkyl-ether method by an alcohol and an acid catalyst (Japanese PatentPublication (A) No. 305546/1992) are illustrated. As to the latter, themethod by reaction with hydrogen peroxide under formic acid (Bull. Chem.Soc. Jpn., 1989, 62, 1652-1657), the method by reaction with Fe(IV)-EDTA ascorbic acids (J. Mol. Catal. 1982, 14, 333-340), the methodby reaction with peracetic acid (Nippon Kagaku Kaishi 1979, 370-374),and the method of synthesis by photo oxidization under Lewis acid (Chem.Lett., 1972, 179-180) are illustrated.

However, the above known methods are generally inferior in a yield and aposition-selectivity. Accordingly, the mixture of regioisomers forms andit is difficult to separate each other so that these methods are notsuitable for preparing the intermediates of pharmaceuticals andagricultural chemicals which require high purity. Expensive reagents andraw materials which are difficult to obtain, are sometimes used andtherefore, these known methods are not satisfied in the industrialproduction.

The present inventors engaged extensively in solving the above problems,and have found a new process for preparation of a catechol derivativealmost without any by-products and in a high yield and that in a highpurity almost without contamination of regioisomers.

DISCLOSURE OF INVENTION

The present invention provides to a process for preparing a catecholderivative represented by the following generic formula (1), ##STR2##and is characterized in preparing the catechol derivative by thefollowing three steps:

(I) a step for preparing a salicylaldehyde derivative represented by thefollowing generic formula (3), ##STR3## by reacting a phenol derivativerepresented by the following formula (2), ##STR4## with a base andparaformaldehyde in the presence of SnCl₂ and/or SnCl₄ in an organicsolvent at 60-85° C. until attaining the conversion to 30-80% and thencompleting the reaction at 95-105° C.;

(II) a step for preparing a formyl ether represented by the followinggeneric formula (4), ##STR5## by treating a salicylaldehyde derivativeof the formula (3) by an alkylating agent in the presence of a base inwater and/or an organic solvent to introduce a hydroxy protective group;and

(III) a step for preparing a catechol derivative represented by theformula (1) by oxidizing a formyl ether of the formula (4) in waterand/or an organic solvent, and then hydrolyzing the product in thepresence of an acid or a base.

In the above formulae (1)-(4), R is alkyl, cycloalkyl, aralkyl, alkoxy,halogen atom, allyl, or aryl, R¹ is a hydroxy protective group, which isselected from known hydroxy protective groups, and said protective groupis preferable one which is not eliminated by oxidation and hydrolysis inthe course of the reaction of the step (III). Examples of saidprotective group are alkyl, benzyl, o-nitrobenzyl, p-methoxybenzyl, andallyl.

The above each step is explained in detail.

In the step (I), as the alkyl in R of a phenol derivative of the formula(2), alkyls blanched or not blanched having 1-4 carbon atoms, such asmethyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, tert-butyl, etc.;as the cycloalkyl in the R, cycloalkyls having 3-6 carbon atoms, such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.; as the aralkylin the R, phenylalkyls having 1-3 carbon atoms in its alkyl portion,such as benzyl, phenethyl, etc.; as the alkoxy in the R, alkyloxyshaving 1-4 carbon atoms in its branched or not branched alkyl portion,such as methyloxy, ethyloxy, n-propyloxy, i-propyloxy, n-butyloxy,sec-butyloxy, tert-butyloxy, etc.; as the halogen atom in the R,chlorine atom, bromine atom, iodine atom, etc.; as the aryl in the R,phenyl, o-tolyl, m-tolyl, p-tolyl, etc., are preferably illustratedrespectively.

The typical examples of the above phenol derivative are o-cresol,2-ethylphenol, 2-cyclopropylphenol, 2-cyclobutylphenol, 2-benzylphenol,2-(phenylethyl)phenol, 2-methyloxyphenol(guaiacol), 2-ethyloxyphenol,2-chlorophenol, 2-bromophenol, 2-iodophenol, 2-allylphenol,2-hydroxybiphenyl, 2-(o-tolyl)phenol, etc.

As the bases used in the step (I), there are preferably illustratedaliphatic trialkylamines having 1-10 carbon atoms in their each alkylportion, such as trimethylamine, triethylamine, tripropylamine,tributylamine, tripentylamine, trihexylamine, triheptylamine,trioctylamine, etc., aromatic amines, such as N,N-dimethylaniline,N,N-diethylaniline, etc., and heterocyclic compounds containing N atom,such as 2,6-lutidine, pyridine, etc.

The reaction in the step (I) is carried out by reacting a phenolderivative, a base and paraformaldehyde in the presence of SnCl₂ and/orSnCl₄ in an organic solvent at 0-85° C. to the conversion of 30-80%,preferably 50-80% and then to complete the reaction at 95-105° C. togive a salicylaldehyde derivative of the formula (3) in a high yield andin a high selectivity.

In regard to the technique converting a phenol derivative into asalicylaldehyde derivative in the above step (I), the process forpreparing a salicylaldehyde derivative by using the same raw materialand the same catalyst as in the step (I) at 90-150° C., preferably 110°C. by one stage is known (Japanese Patent Publication (A) No.34737/1978). However, on the known process, paraformaldehyde used for araw material causes drastically the thermal degradation or thepolymerization reaction preferentially occurs to produce an oligomer asa by-product and therefore, the yield significantly decreases and theposition on which an aldehyde group is introduced varies among o-, m-,and p-positions and the position-selectivity is not enough satisfied.

This invention is based on the finding that the production of anundesirable oligomer as a by-product is controlled and an aldehyde groupis introduced only on the o-position and as a result, an objectivesalicylaldehyde derivative can be obtained in a high yield and a highselectivity, by adopting the method that the aldehydeintroducing-reaction in the step (I) is carried out by two stages underthe specific conditions, and by using this intermediate, the finallyobjective catechol derivative of the formula (I) can be obtained with ahigh purity.

In case that the conversion in the first stage is less than 30%,paraformaldehyde, a raw material causes the thermal degradation and aresulting salicylaldehyde derivative is polymerized withparaformaldehyde to decrease significantly the yield in the secondstage. In case that the conversion is more than 80%, it takes too manyhours in the reaction of the first stage and a resulting salicylaldehydederivative is polymerized with paraformaldehyde to decrease the yield.Therefore, by controlling the reaction of the first stage within theabove mentioned conversion rate at 60-85° C., the reaction is carriedefficiently out and a salicylaldehyde derivative is obtained in a highyield.

In the second stage, in case that the reaction temperature is lower than95° C., it takes too many hours to complete the reaction, and in casethat the reaction temperature is higher than 105° C., the yieldsignificantly decreases due to the degradation of paraformaldehyde, araw material, or the polymerization of a resulting salicylaldehydederivative.

The amount of SnCl₂ and/or SnCl₄ used in the step (I) is 0.025-5 molequivalents to a phenol derivative, a starting material, preferably0.025-1 mol equivalent, and the amount of a base is 0.1-20 molequivalents to said phenol derivative, preferably 0.1-4 mol equivalents.The amount of paraformaldehyde is 2-10 mol equivalent to said phenolderivative, preferably 2-5 mol equivalents.

The organic solvents used are aromatic solvents, such as benzene,toluene, xylene, etc., ethers, such as diethyl ether, tetrahydrofuran,1,4-dioxane, 1,2-dimethoxyethane, diglyme, triglyme, diethylene glycolmonomethyl ether, etc., chlorinated solvents, such as dichloromethane,dichloroethane, chloroform, etc., and a mixture thereof may be alsoused.

A salicylaldehyde derivative thus obtained may be isolated and purifiedby distillation etc., but the product without purification may be usedas a starting material in the next step (II).

The reaction in the step (II) is in obtaining the formyl ether of theformula (4), which is the hydroxy protected product, by reacting asalicylaldehyde derivative prepared according to the above step (I) withan alkylating agent in the presence of a base in water and/or an organicsolvent by the usual manner in order to obtain said compound. As thealkylating agents, halogenated compounds, such as alkyl halide, aralkylhalide, allyl halide, etc., and dialkyl sulfate are illustrated.

As the alkyl halides, there are exemplified alkyl halides having 1-4carbon atoms, such as methyl chloride, methyl bromide, methyl iodide,ethyl chloride, ethyl bromide, ethyl iodide, propyl chloride, propylbromide, propyl iodide, butyl chloride, butyl bromide, butyl iodide,etc.

As the aralkyl halides, there are exemplified phenylalkyl halides inwhich the benzene ring may be substituted by halogen atom, nitro, alkoxyhaving 1-4 carbon atoms, or alkyl having 1-4 carbon atoms and in whichthe alkyl portion has 1-4 carbon atoms, such as benzyl chloride, benzylbromide, benzyl iodide, o-nitrobenzyl chloride, o-nitrobenzyl bromide,o-nitrobenzyl iodide, p-methoxybenzyl chloride, p-methoxybenzyl bromide,p-methoxybenzyl iodide, etc.

As the allyl halides, there are illustrated allyl chloride, allylbromide, etc. As the dialkyl sulfates, there are illustrated dialkylsulfates in which each alkyl has 1-4 carbon atoms, such as dimethylsulfate, diethyl sulfate, etc.

The amount of the alkylating agent is 1-5 mol equivalents to asalicylaldehyde derivative, preferably 1-3 mol equivalents.

As the bases used in the step (II), there are preferably illustratedalkali metal or alkaline earth metal hydrides, oxides, hydroxides,carbonates, or hydrogen carbonates, such as inorganic bases, such aspotassium hydride, sodium hydride, calcium hydride, potassium oxide,sodium oxide, calcium oxide, potassium hydroxide, sodium hydroxide,potassium carbonate, sodium carbonate, calcium carbonate, potassiumhydrogencarbonate, sodium hydrogencarbonate, calcium hydrogencarbonate,organic bases, such as alkoxides (e.g. potassium methoxide, potassiumethoxide, sodium methoxide, sodium ethoxide, etc.), and alkyllithiums(e.g. methyllithium, ethyllithium, n-butyllithium, sec-butyllithium,tert-butyllithium, phenyllithium, etc.)

The amount of the above base is 1-5 mol equivalents to a salicylaldehydederivative, preferably 1-3 mol equivalents.

The solvents used in step (II) are aromatic solvents, such as benzene,toluene, xylene, etc., ethers, such as diethyl ether, tetrahydrofuran,1,4-dioxane, 1,2-dimethoxyethane, diglyme, triglyme, diethylene glycolmonomethyl ether, etc., chlorinated solvents, such as dichloromethane,dichloroethane, chloroform, etc., aprotic solvents, such asN,N-dimethylformamide, dimethyl sulfoxide, sulfolane,hexamethylphosphoramide, etc., ketones, such as acetone, methyl ethylketone, methyl iso-propyl ketone, etc., alcohols, such as methanol,ethanol, i-propanol, etc., acetonitrile, water, and so on. A mixturethereof may be used.

The reaction temperature in the step (II) is preferably from 20° C. tothe boiling point of the solvent. In case that the reaction temperatureis too low, the reaction rate decreases significantly and the yielddecreases. Therefore, the low temperature should be avoided.

The formyl ether thus prepared may be isolated or purified, but theproduct without purification may be used as a starting material in thenext step.

In this invention, in the step (III), the object compound, catecholderivative is obtainable by oxidizing a formyl ether with a oxidizingagent in water and/or an organic solvent, followed by hydrolysis in thepresence of a base or an acid, but when the oxidation is carried out inthe presence of a base or an acid, the hydrolysis occurs together withthe oxidation to obtain the objective compound at once. (J. Org. Chem.1984, 49, 4740-4741, Japanese Patent Publication (A) No.166637/1985) Inthis case once a formate of the following formula (5) or its equivalentforms, but the product seems to be changed into a catechol derivative atonce. ##STR6##

wherein R and R¹ are the same as defined in the formula (1).

The oxidizing agents used in the step (III) are preferably peroxides, astypical ones, such as hydrogen peroxide, m-chloroperbenzoic acid,peracetic acid, perbenzoic acid, monoperoxyorthophthalic acid,monoperoxymaleic acid, peroxyformic acid, p-nitroperbenzoic acid,tert-butylperoxide, etc.

The amount of the oxidizing agent is 1-5 mol equivalents to a formylether, preferably 1-3 mol equivalents.

The acids used in the step (III) are mineral acids, such as hydrochloricacid, sulfuric acid, nitric acid, phosphoric acid, etc., acidic salts ofa mineral acid, such as sodium hydrogensulfate, potassiumhydrogensulfate, sodium dihydrogenphosphate, etc., organic acids, suchas formic acid, acetic acid, methanesulfonic acid, p-toluenesulfonicacid, etc. As the bases, there are illustrated the same inorganic basesor organic bases as used in the step (II). The amount of the acid or thebase is 0.1-5 mol equivalents to a formyl ether, preferably 0.1-3 molequivalents.

The solvents used in the step (III) are the same organic solvent as usedin the step (I), such as aromatic solvents, ethers, chlorinated solventsand alcohols (e.g. methanol, ethanol, i-propanol, etc.), and water. Amixture thereof may be used.

The reaction temperature on oxidation and hydrolysis in the step (III)is from 0° C. to the boiling point of the solvent used, but the lowtemperature cause to decrease the reaction rate significantly andtherefore, it is not practical.

BEST MODE FOR CARRYING OUT INVENTION

According to this invention, the objective compound is prepared via theabove mentioned three steps, but the compound prepared by the each stepwithout isolation or purification is used in the next step reaction andsuch the process is also included in this invention.

In the following examples, the examples in which the catalyst in thestep (I) was changed and the reaction temperatures in the first stageand the second stage were changed were shown, and the comparativeexample in which the reaction in the first stage was carried out at thelower temperature than at the temperature limited by this invention wasshown. And the comparative example in which the reaction was carried outonce (without division into 1st and 2nd stages) was also shown.

As the examples in the step (II), the examples in which a base, analkylating agent and a solvent were respectively changed were shown. Asthe examples in the step (III), the examples in which oxidation andhydrolysis under the acidic conditions was carried out at once, and inwhich oxidation and hydrolysis were separately or independently carriedout were shown.

In the following examples, the conversion in the step (I) was calculatedby the following equation.

    Conversion (%)=area of HPLC on a salicylaldehyde derivative/ area of HPLC on a phenol derivative×100

The above each area is the area of liquid chromatogram which wasobtained by the following conditions:

Analytical conditions

Column: Daiso Pack SP-120-5-ODS-AP (Daiso Co., Ltd.)

Mobile phase: phosphoric acid-acetonitrile-water=0.0001:60:40(volumeratio)

Flow rate: 1.0 ml/min.

Detection: absorbance at 210 nm

EXAMPLE

[I] Process for preparation of salicylaldehyde

1-(1)

o-Cresol 20.0 g (185 mmol) was dissolved in toluene 400 ml and theretowas added 2,6-lutidine 18.4 g (171 mmol). SnCl₄ 4.8 g (18 mmol) wasadded to the mixture and the mixture was stirred for 30 min. at 20° C.Thereto was added paraformaldehyde (purity: 95 weight %) 12.9 g (409mmol) and the mixture was stirred at 80° C. for 5 hours to theconversion of 78%. And the reaction was kept for 10 hours at 100° C. toconfirm the disappearance of the raw material, o-cresol. The reactionsolution was cooled to room temperature, extracted with water-toluene ina separatory funnel and the organic layer was dried over anhydrousmagnesium sulfate and dried in vacuo to give2-hydroxy-3-methylbenzaldehyde 24.9 g (yield: 99%, selectivity: 99%).

1-(2)

By using SnCl₂ 3.5 g (18 mmol) instead of SnCl₄ 4.8 g, in the samemanner as in the above 1-(1), except for to the conversion of 70%, therewas obtained 2-hydroxy-3-methylbenzaldehyde 24.4 g (yield: 97%,selectivity: 98%).

1-(3)

In the same manner as in the above 1-(1), except for at 65° C. for 7hours and to the conversion of 51% in the first stage and at 95° C. for13 hours in the second stage, there was obtained2-hydroxy-3-methylbenzaldehyde 24.4 g (yield: 97%, selectivity: 99%).

Comparative 1-(1)

In the same manner as in the above 1-(1), except for at 40° C. for 7hours and to the conversion of 25% in the first stage and at 95° C. for13 hours in the second stage, there was obtained2-hydroxy-3-methylbenzaldehyde 10.5 g (yield: 42%, selectivity: 75%).

Comparative 1-(2)

In the same manner as in the above 1-(1), except for at 100° C. for 7hours and to the conversion of 99% in the first stage, there wasobtained 2-hydroxy-3-methylbenzaldehyde 12.0 g (yield: 48%, selectivity:62%)

Comparative 1-(3)

In the same manner as in the above 1-(1), except for at 70° C. for 35hours and to the conversion of 99% in the first stage, there wasobtained 2-hydroxy-3-methylbenzaldehyde 11.7 g (yield: 47%, selectivity:60%)

[II] Process for preparation of formyl ether

2-(1)

A solution of 2-hydroxy-3-methylbenzaldehyde 20.0 g (147 mmol) preparedby the above 1-(1) in dimethylformamide (DMF) (100 ml) was added to thesuspension of sodium hydride 6.5 g (163 mmol) with purity 60% and DMF(40 ml) under ice-cooling. After completion of emission of hydrogen gas,benzyl bromide 25.0 g (147 mmol) was dropped to it in a ice bath. Thereaction mixture was stirred for 4 hours at 20° C. After thedisappearance of the raw material, water was added to the reactionmixture and it was extracted with methylene chloride. The organic layerwas dried over anhydrous magnesium sulfate, the solvent was removed invacuo and the residue was purified by silica gel chromatography(n-hexane-ethyl acetate) to give 2-benzyloxy-3-methylbenzaldehyde 29.9 g(yield: 91%).

2-(2)

2-Hydroxy-3-methylbenzaldehyde 20.0 g (147 mmol) prepared by the above1-(1) was dissolved in dimethylformamide (DMF) (100 ml) and to thesolution was added potassium carbonate 31.0 g (221 mmol) and thereto wasdropped benzyl bromide 25.0 g (147 mmol). The reaction mixture wasstirred for 2 hours at 20° C. After disappearance of the raw material,the reaction mixture was filtrated and the solvent was removed in vacuoand the residue was purified in the same manner as in the above 2-(1) togive 2-benzyloxy-3-methylbenzaldehyde 24.2 g (yield: 73%).

2-(3)

In the same manner as in the above 2-(2) except for dissolving in methylethyl ketone (MEK) 100 ml instead of DMF 100 ml, there was obtained2-benzyloxy-3-methylbenzaldehyde 24.9 g (yield: 75%).

2-(4)

In the same manner as in the above 2-(2) except for dissolving inacetonitrile 100 ml instead of DMF 100 ml, there was obtained2-benzyloxy-3-methylbenzaldehyde 25.4 g (yield: 77%).

2-(5)

In the same manner as in the above 2-(2) except for using benzylchloride 18.6 g (147 mmol) instead of benzyl bromide 25.9 g, and at 50°C. (reaction temperature), there was obtained2-benzyloxy-3-methylbenzaldehyde 25.9 g (yield: 79%).

[III] Process for preparation of catechol derivative

3-(1)

2-Benzyloxy-3-methylbenzaldehyde prepared by the above 2-(1) 20.0 g(88.4 mmol) was dissolved in methanol 100 ml and thereto was addedsulfuric acid 20.0 g (203 mmol) and then added 30% hydrogen peroxide30.1 g (265 mmol). The mixture was refluxed for 2 hours. Afterdisappearance of the raw material, the solution was concentrated invacuo, neutralized with a saturated sodium bicarbonate solution andextracted with methylene chloride. The solvent was removed in vacuo andthe residue was purified by silica gel chromatography (n-hexane-ethylacetate) to give 2-benzyloxy-3-methylphenol 13.3 g (yield: 70%).

3-(2)

2-Benzyloxy-3-methylbenzaldehyde prepared by the above 2-(1) 20.0 g(88.4 mmol) was dissolved in methylene chloride 100 ml and thereto wasadded m-chloroperbenzoic acid 16.8 g (97.2 mmol). The mixture wasreacted at 20° C. under stirring for 10 hours. After disappearance ofthe raw material, the solution was neutralized with a saturated sodiumbicarbonate solution and extracted with methylene chloride. To theextract (2-benzyloxy-3-formyloxytoluene) was added a 10% sodiumhydroxide solution 38.9 g (97.2 mmol) in the ice bath and the mixturewas stirred for 3 hours. The reaction mixture was neutralized with a 5%hydrochloric acid solution and extracted with methylene chloride. Thesolvent was removed in vacuo and the residue was purified in the samemanner as in the above mentioned 3-(1) to give2-benzyloxy-3-methylphenol 16.7 g (yield: 88%).

Industrial Applicability

According to this invention, by carrying out the reaction of the step(I) in two stages under the specified conditions, the degradation ofparaformaldehyde and the polymerization of paraformaldehyde in thereaction can be controlled and the intermediate without contamination ofregioisomers can be obtained in a high yield, and thereby, the finallyobjective compound, a catechol derivative can be obtained with a highpurity.

We claim:
 1. A process for preparing a catechol derivative representedby the following generic formula (1), ##STR7## is characterized inpreparing the catechol derivative by the steps consisting essentiallyof(I) a step for preparing a salicylaldehyde derivative represented bythe following generic formula (3), ##STR8## at a yield of at least 95%,by reacting a phenol derivative represented by the following formula(2), ##STR9## with a base and paraformaldehyde in the presence of SnCl₂and/or SnCl₄ in an organic solvent at 60-85° C. until attaining theconversion to 30-80% and then by completion of the reaction at 95-105°C.; (II) a step for preparing a formyl ether represented by thefollowing generic formula (4), ##STR10## by treating a salicylaldehydederivative of the formula (3) by an alkylating agent in the presence ofa base in water and/or an organic solvent to introduce a hydroxyprotective group; and (III) a step for preparing a catechol derivativeof the formula (1) by oxidizing a formyl ether of the formula (4) inwater and/or an organic solvent, and then hydrolyzing the product in thepresence of an acid or a base, wherein in the above formulae (1)-(4), Ris alkyl, cycloalkyl, aralkyl, alkoxy, halogen atom, allyl, or aryl, R¹is a hydroxy protective group.
 2. The process for a catechol derivativeclaimed in claim 1, wherein a base used in the step (I) is a baseselected from aliphatic trialkylamines, aromatic amines and heterocycliccompounds containing N atom.
 3. The process for a catechol derivativeclaimed in claim 2, wherein the aliphatic trialkylamine is an amineselected from trialkylamines in which each alkyl portion has 1-10 carbonatoms, the aromatic amine is N,N-dimethylaniline or N,N-diethylaniline,and the heterocyclic compound containing N atom is 2,6-lutidine orpyridine.
 4. The process for a catechol derivative claimed in claim 1,wherein the base used in the step (II) is an alkali metal or alkalineearth metal hydride, oxide, hydroxide, carbonate or bicarbonate, or anorganic base.
 5. The process for a catechol derivative claimed in claim1, wherein the alkylating agent used in the step (II) is a halogenatedcompound selected from alkyl halides, aralkyl halides and allyl halides,or a dialkyl sulfate.
 6. The process for a catechol derivative claimedin claim 1, wherein the oxidation agent used in the step (III) is aperoxide.
 7. The process for a catechol derivative claimed in claim 1,wherein the oxidation agent is an oxidation agent selected from hydrogenperoxide, m-chloroperbenzoic acid, peracetic acid, perbenzoic acid,monoperoxyorthophthalic acid, monoperoxymaleic acid, peroxyformic acid,p-nitroperbenzoic acid, and tert-butylperoxide.
 8. The process for acatechol derivative claimed in claim 1, wherein the acid used in thestep (III) is a mineral acid selected from hydrochloric acid, sulfuricacid and nitric acid, or an organic acid selected from formic acid,acetic acid, methanesulfonic acid and p-toluenesulfonic acid.
 9. Theprocess for a catechol derivative claimed in claim 1, wherein the baseused in the step (III) is an alkali metal or alkaline earth metalhydride, oxide, hydroxide, carbonate or bicarbonate, or an organic base.